Balb/cCrgl mice and their syngeneic mammary tumors induced by 7, 12-dimethylbenxanthracene are free of whole virions of mammary tumor virus (MTV). Some MTV-associated antigen(s) appear to be expressed and splenocytes of these mice also react to MTV. This natural immunity correlates with a very low indidence of spontaneous mammary tumors (SMT). In contrast, Balb/cfC3H mice contain MTV and possess a high incidence of SMT in which MTV particles can be detected. Splenocytes of these mice do not react significantly to MTV except after development of our transplantation with MTV-positive mammary tumors. Both lines of mice show similar patterns of cell mediated immune reactivities to their respective tumor antigens: No response prior to transplantation, peaked reactivities 2-3 weeks after transplantation and loss of activity when tumors reach a mximum size. A similar pattern is also observed with spleen cells of Balb/cfC3H exposed to MTV antigens in vitro, indicating that this is a de novo sensitization. In Balb/cCrgl there is a dissociation of responses to tumor and viral antigens. The intensity of responses to tumor antigen depends on tumor size as noted above, while the responses to MTV are constant in normal and tumor-bearing animals at all stages. The importance of this natural immunity seen in Balb/c mice has been explored with in vivo studies. Inoculation of MTV-positive SMT cells in MTV-negative Balb/cCrgl and in MTV-postive Balb/cfC3H mice resulted in lower incidence of tumors in the former. Moreover, the time of appearance and the progression of tumor were delayed in the MTV-negative mice. Another line of evidence supporting the relevance of this natural immunity comes from the high incidence of SMT seen in hereditarily asplenic Balb/c mice. While the sister mice with spleens from this colony have an incidence of 12% SMT appearing by 16 months of age, the asplenic females have an incidence of 46% SMT with a mean age of appearance of 10 months. On the basis of these observations we proposee to identify, characterize and isolate the immunological relevant cells known to respond to either viral or tumor antigens and to use them in adoptive transfer studies. This immunotherapeutic approach will be studied with the aim of achieving protection of mice with a high incidence of SMT. Since the relevance of th (Text Truncated - Exceeds Capacity)